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PubMed2002

The meaning response and the ethics of avoiding placebos.

Because the "placebo effect" seems to result from "deception," it is often disparaged and despised. Rethinking this and realizing that these benefits flow largely from the meaning of medical encounters (and are far better understood as "meaning responses"); realizing that there need be no deception to elicit them and that they are often very desirable, engaging fundamental human biological pathways, puts the ethical dilemma in a new light. It seems unethical to avoid--to evade--coming to a full understanding of how meaning can so profoundly improve human well-being.

Analgesia↗
PubMed2005

Neural monoaminergic mediation of the effect of St. John's wort extract on prepulse inhibition of the acoustic startle response in rats.

Prepulse inhibition (PPI) of startle response is a valuable paradigm for sensorimotor gating processes by which an organism filters sensory information. Disruption of PPI is evident in schizophrenia and Huntington's disease among other neuropsychiatric disorders characterized by sensorimotor gating deficit. In such disorders, increased brain monoamines' transmission was suggested to underlie PPI disruption. The effect of St. John's wort extract on PPI of startle response is yet to be investigated despite research findings indicating augmented levels of brain monoaminergic function after acute administration of the extract. In this study, the effect of acute oral administration of St. John's wort extract (62.5, 125, 250 and 500 mg/kg) was tested on PPI of an acoustic startle response in rats. A disruption of PPI resulted after the administration of the highest dose of the extract and therefore its effect on dopaminergic, serotonergic and noradrenergic neurotransmission was investigated in a number of rat brain areas involved in mediation of PPI response. Results demonstrated that 500 mg/kg of the extract augmented dopaminergic transmission in the thalamus together with elevating noradrenergic transmission in both brainstem and hippocampus. In addition, increased serotonin levels in brainstem, thalamus, cortex and hippocampus were evident after administration of the same dose of the extract. It was therefore concluded that St. John's wort extract (500 mg/kg) reduced PPI response possibly through enhancing monoaminergic transmission in brainstem, thalamus, cortex and/or hippocampus. Clinical investigations are therefore needed to determine whether St. John's wort extract may affect sensorimotor gating in both schizophrenia and Huntington's disease.

Acoustic Stimulation↗
PubMed2001

Adverse reactions to St John's Wort.

OBJECTIVE: To report 2 cases of adverse reactions to St John's wort, a popular herbal treatment for depression. METHOD: We present 2 case histories and review the existing literature regarding St John's wort. RESULTS: St John's wort may cause serotonin syndrome in sensitive patients. In addition, St John's wort may be associated with hair loss. CONCLUSIONS: For clinical reasons, it is important to recognize and report adverse reactions to herbal remedies and to document that these treatments have side effects commensurate with their potent action on brain neurochemistry.

Adult↗
PubMed2006

Systematic overview of drug interactions with antidepressant medications.

OBJECTIVE: Antidepressants are commonly used drugs with potential for numerous drug interactions. This study aims to systematically review the literature on drug interactions with antidepressants. METHODS: We searched MEDLINE (1966 to November 2003) and EMBASE (1980 to 2003), using the heading drug interactions combined with individual antidepressant names. We restricted searches to English-language articles and human studies. We screened drug interaction texts and review articles for relevant studies. We included articles reporting original human data on drug interactions with antidepressants commonly used in North America. Articles were independently evaluated by 2 reviewers on clinical effect, clinical significance, and quality of evidence. Discrepancies were resolved by consensus. RESULTS: There were 904 eligible interactions, involving 9509 patients, for a total of 598 summary interactions. Of these, 439 (73%) demonstrated an interaction, 148 (25%) had no effect, and 11 (2%) had conflicting evidence. For 510 interactions (85%), the quality of evidence was poor. It was fair for 67 (11%) interactions and good for 10 (2%) interactions. There were no interactions with excellent quality of evidence. There were 145 (24%) interactions of major clinical significance. These were predominantly hypertensive emergencies and serotonin syndrome. Most interacting drugs had central nervous system (CNS) activity. As expected, monoamine oxidase inhibitors (MAOIs) appear to be the most problematic family in terms of potential for serious drug interactions. CONCLUSIONS: Drug interactions with antidepressants are an important cause for concern, but this concern is based primarily on poor evidence. We recommend caution when combining antidepressants with other CNS drugs, particularly when coadministering MAOIs with other substances.

Cytochrome P-450 Enzyme System↗
PubMed2003

Nurses and nutraceuticals. Knowledge and use.

Increasing use of herbal products by the American public should prompt nurses to routinely address herbal use during patient interactions. However, whether nurses possess the knowledge required to discuss risks and benefits of herbal use with patients is unknown. This study was undertaken to investigate registered nurses' knowledge about and use of five common herbal products: ginkgo, St. John's wort, ginseng, garlic, and echinacea. One hundred forty-nine (30%) of 500 randomly selected nurses responded to a mailed questionnaire addressing the frequency of use, purpose, side effects, and interactions of the above products. Most respondents had neither used nor suggested use of the products. Respondents were relatively unfamiliar with product characteristics, although somewhat more familiar with purpose than with side effects or interactions. No knowledge differences were identified according to practice area or number of years in practice, but differences were noted according to educational level and use of specific products.

Adult↗
PubMed2004

Images of nature in relation to mood modifying medicines: a user perspective.

Appeals to nature are common, however the term is associated with multiple or even oppositional meanings. This article explores the way nature is evoked and references are made to chemicals in relation to both prescribed and herbal mood modifying medicines. Data are drawn from 23 interviews with people who were taking, had been offered or had taken, either or both prescribed and herbal mood modifying medicines. Fifteen of the 23 respondents used the ideas of natural and chemical when discussing their medicine taking decisions. Rather than a dichotomy between prescribed and herbal remedies in relation to the ideas of natural and chemical, the notion of translations, and ideas concerning risk, are suggested as more appropriate for understanding how different treatments are assessed.

Adolescent↗
PubMed2001

St John's wort: a hidden risk for transplant patients.

Herbal medications may cause prescription drug interactions in transplant recipients. After 2 of our kidney transplant recipients started self-medicating with St John's wort, their cyclosporine concentrations were consistently documented to be subtherapeutic. While on St John's wort, one patient developed acute rejection possibly due to low cyclosporine concentrations. Termination of St John's wort returned both patients' cyclosporine concentrations to therapeutic values. Based on the Naranjo Adverse Drug Reaction Probability Scale, our report would achieve a "probable" score, which supports the existence of a St John's wort-cyclosporine adverse drug interaction. St John's wort may induce cytochrome P-450 3A4 activity and/or P-glycoprotein expression, which are both involved in the metabolism and absorption of cyclosporine. Patients using St John's wort concomitantly with cyclosporine or other medications with similar absorption and/or metabolism to cyclosporine need close monitoring. Transplant coordinators are in a critical position to educate transplant recipients about the potential risks of herbal medication usage.

ATP Binding Cassette Transporter, Subfamily B, Mem↗
PubMed2004

Use of antidepressant drugs in transplant recipients.

Depression is the most prevalent psychiatric disorder in transplant recipients and may lead to noncompliance and negative outcomes without psychosocial and pharmacologic interventions. The pharmacologic treatment of depression in this patient population is complicated by complex immunosuppressant drug regimens and multiple potential drug interactions that can adversely affect the newly transplanted organs. This review provides a brief overview of the currently available antidepressant medications and highlights the clinically important features each class of agents in transplant recipients. Newer agents selective serotonin reuptake inhibitors, venlafaxine, bupropion, nefazodone, and mirtazapine are discussed as well as tricyclic antidepressants and monoamine oxidase inhibitors. A brief discussion of St. John's wort and its impact on posttransplant drug therapy is also included.

Adrenergic alpha-2 Receptor Antagonists↗
PubMed2005

State of the science: hot flashes and cancer. Part 2: management and future directions.

PURPOSE/OBJECTIVES: To critically evaluate and synthesize intervention research related to hot flashes in the context of cancer and to identify implications and future directions for policy, research, and practice. DATA SOURCES: Published, peer-reviewed articles and textbooks; editorials; and computerized databases. DATA SYNTHESIS: Although a variety of pharmacologic and nonpharmacologic treatments are available, they may not be appropriate or effective for all individuals. CONCLUSIONS: The large and diverse evidence base and current national attention on hot flash treatment highlight the importance of the symptom to healthcare professionals, including oncology nurses. IMPLICATIONS FOR NURSING: Using existing research to understand, assess, and manage hot flashes in the context of cancer can prevent patient discomfort and improve the delivery of evidence-based care.

Antidepressive Agents↗
PubMed2004

Quantitative characterization of direct P-glycoprotein inhibition by St John's wort constituents hypericin and hyperforin.

The ATP-binding cassette transporter P-glycoprotein (P-gp) exerts a critical role in the systemic disposition of, and exposure to, lipophilic and amphipathic drugs, carcinogens, toxins and other xenobiotics. The ability of P-gp to transfer a wide variety of structurally unrelated compounds from the cell interior across the membrane bilayer remains intriguing. Since natural product chemicals in the widely consumed St John's wort appear to exert antidepressant effects by an unknown mechanism, the constituents are frequently studied for interactions with various biomacromolecules as well as cytotoxins or isolated cells. The drug interactions caused by this widely used herbal remedy are under-appreciated. Various clinical interactions have been observed upon the co-administration of St John's wort, and P-gp and CYP3A4 have been indicted as the cause. We characterized several St John's wort constituents for their interaction with P-gp and their specific effects on the P-gp export activity of several marker substrates. Two of these constituents, hyperforin and hypericin, inhibit the active efflux of the fluorescent markers daunorubicin (IC(50) approximately 30 microM) and calcein-AM. Herein, we show in-vitro results that can both explain the competing clinical observations of initial elevated exposure of P-gp substrate drugs (P-gp inhibition) followed by under-exposure (P-gp induction) when St John's wort is co-administered, and provide a further warning against unchecked co-administration of drugs with St John's wort.

ATP Binding Cassette Transporter, Subfamily B, Mem↗
PubMed2002

Biorelevant dissolution testing of St John's wort products.

In contrast to chemically defined drugs, most herbal medicinal products (HMPs) are poorly characterized in terms of their pharmaceutical properties. In many cases it is assumed that the plant extract as a whole is the active moiety, since it is often difficult to identify the individual components responsible for the pharmacological activity and even more difficult to assess synergies among the various components. However, where the active components have been identified, it should be possible to compare products with respect not only to content uniformity but also to their biopharmaceutical properties. The aim of this study was to investigate and compare the dissolution characteristics of several St John's wort products under biorelevant conditions. Components of St John's wort known, or suspected, to play a role in its antidepressant activity include phloroglucines, naphthodianthrones and the flavonoids. Since these groups have a broad spectrum of polarity and solubility, dissolution was studied for representative compounds from each group. Although the labelling indicates that several of the products studied should be pharmaceutically equivalent, dissolution under biorelevant conditions revealed that they have quite different release profiles and cannot be considered switchable. It was concluded that biorelevant dissolution testing can be a powerful tool for comparing HMPs as well as synthetically produced drug products.

Antidepressive Agents↗
PubMed2005

Quantitative analysis of the major constituents of St John's wort with HPLC-ESI-MS.

A method was developed to profile the major constituents of St John's wort extracts using high-performance liquid chromatography-electrospray mass spectrometry (HPLC-ESI-MS). The objective was to simultaneously separate, identify and quantify hyperforin, hypericin, pseudohypericin, rutin, hyperoside, isoquercetrin, quercitrin and chlorogenic acid using HPLC-MS. Quantification was performed using an external standardisation method with reference standards. The method consisted of two protocols: one for the analysis of flavonoids and glycosides and the other for the analysis of the more lipophilic hypericins and hyperforin. Both protocols used a reverse phase Luna phenyl hexyl column. The separation of the flavonoids and glycosides was achieved within 35 min and that of the hypericins and hyperforin within 9 min. The linear response range in ESI-MS was established for each compound and all had linear regression coefficient values greater than 0.97. Both protocols proved to be very specific for the constituents analysed. MS analysis showed no other signals within the analyte peaks. The method was robust and applicable to alcoholic tinctures, tablet/capsule extracts in various solvents and herb extracts. The method was applied to evaluate the phytopharmaceutical quality of St John's wort preparations available in the UK in order to test the method and investigate if they contain at least the main constituents and at what concentrations.

Anthracenes↗
PubMed2004

Apocynum venetum extract does not induce CYP3A and P-glycoprotein in rats.

We investigated the effect of Apocynum venetum L. extract (AV) on the activity of cytochrome P450 (CYP) 3A and P-glycoprotein (P-gp). The plasma concentration of nifedipine (NF), which is a substrate for CYP3A, did not change after oral administration with AV (3.3 mg/kg). Also, AV (3.3 and 33 mg/kg) did not affect the intestinal absorption of NF. In the rats treated with multiple administrations (15 mg/kg/d) of St. John's wort extract (SJW) for 2 weeks, the plasma concentration of NF after oral administration was significantly decreased. On the other hand, there was no significant differences in the pharmacokinetic parameters of NF between AV-treated (3.3 mg/kg/d) and none-treated rats. Furthermore, the intestinal absorption of methylprednisolone, which is a substrate for P-gp, was not affected by AV treatment for 2 weeks. These results suggest that, unlike SJW, the recommended dose of AV (3.3 mg/kg/d) would not influence hepatic CYP3A and intestinal P-gp in rats.

ATP Binding Cassette Transporter, Subfamily B, Mem↗
PubMed2005

Time-dependent induction of midazolam-1-hydroxylation enzymes in rats treated with St. John's wort.

Time-dependent effects of St. John's wort (SJW) on midazolam 1-hydroxylation were investigated in Wistar rats. Wistar rats treated with SJW (1000 mg/kg/d) for 1, 3, and 7 d were administered midazolam orally at a dose of 10 mg/kg. Oral clearance of midazolam in the SJW treated rats increased time dependently, and was significant after 7 d of treatment with SJW. The midazoram-1-hydroxylation activity in liver microsomes obtained from the SJW treated rats was significantly higher than in the control group. Linear correlation was observed between oral clearance and midazolam-1-hydroxylation activity in the liver microsomes, suggesting that CYP3A induction in liver mainly decreased the midazolam concentration in plasma. Immunoblotting revealed that the protein amount of CYP3A was induced within 3 d of SJW treatment. Since the midazolam-1-hydroxylation activity continuously increased for at least 7 d, the induction of CYP3A by SJW continued to cause interactions with drugs metabolized by CYP3A. It is important for persons receiving SJW for an extended time to consider its interactions with prescription drugs.

Animals↗